Antibiotic Resistance: Alarm bells ring louder than ever

Though international focus is turning to antimicrobial resistance and incentives are being provided for research into new drugs, there are many hurdles to be jumped before a blockbuster can be discovered and developed in this challenging field.

With UK Prime Minister David Cameron talking of a
return to the “dark ages” and Professor Sally Davies, the UK Chief Medical
Officer, speaking of “the apocalypse”, 2014 was the year where antibiotics and
the threat of antimicrobial resistance (AMR) became a hot topic in the
mainstream media. While this has been a growing discussion point for some time in
the healthcare, scientific and pharma communities, the general public face the very
real prospect of drugs widely relied on in day-to-day use and routine medical
procedures no longer being able to cure simple bacterial infections.

How can this be prevented?
AMR is a complex, global issue and corrective action is
only possible if we accurately know and understand what is happening, where and
why, at every level. To this end, the World Health Organisation (WHO) has been
monitoring the situation for over two decades and publishing numerous reports
and guidelines, the latest being Antimicrobial Resistance
- Global Report on Surveillance 2014.
Armed with this understanding, the following issues
can be more effectively addressed:

1.
Prevent the need for antibiotics. Immunisation programmes engender immunity and make
people less susceptible to pathogens. Implementing educational programmes that
promote better hygiene and sanitation at a global level, but especially for
developing countries, automatically reduces incidences of bacterial infection. 2. Prevent the misuse of
antibiotics at all levels. Likewise, increased
education needs to be introduced at an individual patient and health care
professional (HCP) level, but should also be a national government/health policy.
Antibiotics are also used in agriculture and livestock food production, which
can facilitate resistance and is a sector that requires great scrutiny. Further
to education, international government agreements are required that set
standards/targets for monitoring and reducing antibiotic use, much as has been
seen with CO2 emissions.3. Accurate use of the
correct antibiotic. When antibiotic use is
necessary, a more personalised approach is needed, whereby the specific strain
of pathogen is identified and the most appropriate antibiotic is administered. 4. Development of new drugs. While the above steps will go a considerable way to
dealing with AMR as a whole, there is still an urgent need for new and
effective treatments. Challenges of antibiotic developmentThere have been few
new classes of antibacterial discovered in the last 30 years, although the
recent publication in Nature on the
discovery of teixobactin may prove to be a ‘game changer’. So, if the need for
new antibiotics has been widely recognised for so long, why has big pharma not provided
the breakthrough?
While the obvious
solution would be to invest more in research to discover new antimicrobials, the
reality is that this is as challenging scientifically as it is unrewarding economically.
Even leaving aside the prohibitive cost of bringing an antimicrobial to market –
thought to be upwards of £750 million – antibiotics have become less and less attractive for big pharma
for a variety of reasons. First, bacterial infections tend to be short term,
hence they are much less profitable than chronic illnesses where medication
needs to be taken for life.
“The mature
nature of the market means the majority of drugs are cheap-to-produce generics,
which would make it difficult for a new drug to be seen as cost effective”

Further, the mature nature
of the market means the majority of drugs are cheap-to-produce generics which would
make it difficult for a new drug to be seen as cost effective. The recent
economic climate has made many companies more risk averse and, as any new blockbuster
antibiotic faces the prospect of resistance developing and the possibility of guidelines
which restrict its use, it is no wonder pharma companies have been reluctant to
invest. Without greater financial incentives to tempt big pharma to start investing
more heavily in antibiotics research, such as extending patents or guaranteed
returns on investment, it is hard to see where new drug breakthroughs will come
from.
Academia, university spin-offs and small start-ups are
the best hope – an approach which complements the acquisition pipeline model currently
operated by many pharma companies since the financial downturn. This allows
others to assume the inherent risks of early-stage R&D and big pharma to
leverage their know-how and infrastructure to bring to market those molecules
that do have promise. Plus, recent financial incentives have been encouraging these
smaller players, as exemplified by the £10 million 2014 Longitude Prize.
What form might these new breakthroughs take?
The mainstay of recent endeavours has been to
genetically engineer existing products so that they are slightly different in
order to circumvent resistance mechanisms and, while the returns are likely to
be small, it is a relatively safer and easier approach. Another angle is the
development of small molecules that can be administered in conjunction with
antimicrobials to prevent resistance mechanisms such as efflux. In the area of personalised
medicine, work is ongoing to develop quick and simple tests to identify the
strain of bacteria.
But the biggest reward remains the discovery of a new
class of antibiotic, which is most likely to come from as yet undiscovered
strains of bacteria, from rainforests or even the soil beneath our feet. Even
when found, any bacteria must be able to be cultured and tested against known
pathogens to determine the extent of any antibiotic properties. And, after all
this, it still has to be tested for safe use in humans and be cost effective to
produce.
So what is the answer?Bacterial infection has no political allegiance, no
geographic limit and is indiscriminate and merciless in its own pursuit for
survival. AMR must be kept at bay! Only by working together and taking responsibility at patient, HCP, pharma
company, national and international government levels, can we maintain the low rates
of mortality related to bacterial infection that we have become so accustomed
to and complacent about.

About the author:Christophe Homer PhD is an
account manager at Cello Health Insight.
He can be contacted at chomer@cellohealth.com